A Phase I Dose Escalation and Dose Expansion Study to Investigate the Pharmacokinetics and Safety of Subcutaneous Durvalumab (IMFINZI-subQ)

AstraZeneca

Status and phase: Not yet enrolling; Phase 1

Conditions: Solid Tumours

Treatments: Drug: IV durvalumab; Drug: Tremelimumab; Drug: SC durvalumab + rHu

Study type: Interventional

Funder types: Industry

Identifiers

NCT07391670

2025-521639-34-00 (Other Identifier)

D907HC00001

Details and patient eligibility

About

The purpose of the study is to determine a subcutaneous (SC: under the skin) durvalumab + recombinant human hyaluronidase (rHu) dose that yields systemic drug exposure similar to intravenous (IV: into the veins) durvalumab administration and to evaluate the pharmacokinetics and safety of SC durvalumab + rHu injection in participants with different types of solid tumours (cancers).

Full description

This is a Phase I, multicentre study that will consist of 2 parts -

• Part 1: Dose Escalation
• Part 2: Dose Expansion

Part 1 may include participants with solid tumours - non-small cell lung cancer (NSCLC), hepatocellular carcinoma (HCC) or limited-stage small cell lung cancer (LS-SCLC). It will further consist of 2 planned dose levels of SC durvalumab - Dose level 1 (DL1) and Dose level 2 (DL2).

Part 2 will include participants with unresectable HCC. It will be initiated once a dose has been identified based on Part 1.

Enrollment: 40 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• An Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Life expectancy of ≥ 12 weeks at enrolment.
• Adequate organ and marrow function.
• Minimum body weight > 30 kg.

Part 1 only:

Locally Advanced Unresectable (Stage III) NSCLC Participants -

• Histological or cytological documented evidence of NSCLC (locally advanced, unresectable, Stage III).
• Must have received at least 2 cycles of platinum-based chemotherapy concurrent with definitive radiation therapy.
• Have not progressed following definitive concurrent chemoradiation.

LS-SCLC Participants -

• Histologically or cytologically documented LS-SCLC (Stage I-III).
• Received 4 cycles of chemotherapy concurrent with radiotherapy, which must be completed within 1 to 42 days prior to enrolment.
• Have not progressed following definitive concurrent chemoradiation.

Part 1 and 2:

Unresectable HCC Participants -

• Unresectable HCC based on histopathological confirmation.
• No prior systemic therapy for unresectable HCC.
• Must not be eligible for locoregional therapy for unresectable HCC.
• Child-Pugh Score class A.
• Measurable disease as defined by RECIST v1.1.

Exclusion criteria

• Active or prior documented autoimmune disease requiring systemic treatment.
• Uncontrolled infection (including human immunodeficiency virus [HIV], hepatitis B or C).
• Prior exposure to immune checkpoint inhibitors.

Part 1 only:

Locally Advanced Unresectable (Stage III) NSCLC Participants -

• Mixed SCLC and NSCLC histology.
• Active pneumonitis or interstitial lung disease requiring systemic therapy.

LS SCLC Participants -

• Mixed SCLC and NSCLC histology.
• Extensive-stage disease.
• History of Grade ≥ 2 pneumonitis.

Part 1 and 2:

Unresectable HCC Participants -

• Hepatic encephalopathy.
• Uncontrolled ascites.
• Active gastrointestinal (GI) bleeding.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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40 participants in 3 patient groups

Part 1: SC Durvalumab DL1

Experimental group

Description:

Participants will receive DL1 of SC durvalumab + rHu followed by IV durvalumab at predefined intervals.

Treatment:

Drug: SC durvalumab + rHu

Drug: Tremelimumab

Drug: IV durvalumab

Part 1: SC Durvalumab DL2

Experimental group

Description:

Participants will receive DL2 of SC durvalumab + rHu followed by IV durvalumab at predefined intervals.

Treatment:

Drug: SC durvalumab + rHu

Drug: Tremelimumab

Drug: IV durvalumab

Part 2: Expansion Cohort, SC Durvalumab Dose Level X

Experimental group

Description:

Participants will receive dose level X (determined from data analysis in Part 1) of SC durvalumab + rHu followed by IV durvalumab at predefined intervals.

Treatment:

Drug: SC durvalumab + rHu

Drug: Tremelimumab

Drug: IV durvalumab